We propose a prospective study to determine the impact of chronic viral hepatitis and methadone on rates of treatment failure of highly active antiretroviral therapy (HAART) among patients with late-stage HIV infection. Prior exposure to mono or combination antiretroviral therapy and lack of adherence to complex HAART regimens are believed lead to HIV-1 resistance and virologic failure of HAART. However, additional co-factors of treatment failure need evaluation. Our preliminary data suggest that chronic viral hepatitis (which may lead to liver intolerance or upregulate HIV-1) may be important. The role of methadone (which may interact with HAART regimens to decrease effectiveness and cause side effects) also merits study. The study population will be 350 patients recruited from the residential health care facilities (RHCFs) in New York City with over 1200 beds devoted to long-term care for patients with late-stage HIV infection; 85 percent are minority men and women; 55 percent have prior experience with a protease inhibitor and 80 percent receive supervised HAART. HAART is administered and monitored by the nursing staff which should limit the impact of noncompliance. Fifty four percent have chronic viral hepatitis and 66 percent have experience with injection drugs (40 percent of whom receive methadone maintenance). Patients will be followed prospectively at 4 and 8 weeks and quarterly thereafter for up to nine months. At the time of study entry, antiretroviral therapeutic decisions will be guided by a combination of careful treatment history, genotypic resistance testing with expert clinical interpretation and treatment recommendations which should limit the impact of HIV-1 resistance for previous treatments. Data collection at research visits will include medical record review (for clinical and routinely collected laboratory parameters, nurse medication administration records), patient interviews (for self-report medication acceptance and medication adherence) and venipuncture (for genotypic resistance testing, additional HIV virologic and immunologic assays, specimen repository for future studies including phenotypic resistance assays and protease inhibitor trough levels). Analysis of the primary outcome, virologic treatment failure (as defined by the AIDS Clinical Trials Group), will be done using survival and longitudinal data analytic techniques. By conducting this study in this unique RHCF setting where adherence is supervised and monitored, and by optimizing antiretroviral treatment decisions, the effects of chronic viral hepatitis and methadone maintenance can be clarified to improve treatment in this and similar populations.